Post-transcriptional regulation of gene expression is influenced by RNA-binding proteins (RBPs) and small non-coding RNAs that bind to conserved mRNA sequences to modulate mRNA processing. These regulatory molecules affect the structural conformation of mRNAs, creating formations like G-quadruplexes (G4s), which alter translation initiation and regulatory-factor site accessibility. Recent studies have highlighted Nuclear factor erythroid 2-related factor 2 (NRF2) as a key regulator of cellular redox homeostasis and cellular response to oxidative stress. An intriguing feature of NRF2 is the structural formation of its 5' untranslated region (UTR), which may promote or inhibit translation initiation depending on the cellular context. In this study with minigenes, we provide in vitro evidence of RNA G4s in the NRF2 mRNA's 5' UTR under basal (no stress) conditions. Achieved via electrophoretic mobility shift assay and fluorescence spectra in the presence of Pyridostatin. Understanding how structural motifs within NRF2 5' UTRs influence mRNA function provides insights into a common molecular mechanism underlying diseases where NRF2 is dysregulated, like cancers, cardiovascular disease, and neurodegeneration, and highlights potential therapeutic avenues through regulation of NRF2.

The early diagnosis of depression is often impeded by the subjectivity inherent in traditional clinical assessments. To advance objective screening, this study proposes a lightweight neural network framework designed to discriminate between pathological depressive states and non-pathological transient negative emotions using EEG signals. Diverging from conventional methods that rely on single-domain features, we construct a comprehensive multi-domain feature space via Wavelet Packet Decomposition. Specifically, the framework integrates frequency (α/β power spectral density ratio), spatial (normalized α-asymmetry), and non-linear (Sample Entropy) attributes to capture the heterogeneous neurophysiological dynamics of depression. To effectively synthesize these diverse features, a multi-head additive attention mechanism is introduced. This mechanism empowers the model to adaptively recalibrate feature weights, thereby prioritizing the most discriminative patterns associated with the disorder. Experimental validation on the DEAP (negative emotion) and HUSM (major depressive disorder) datasets demonstrates that the proposed method achieves a classification accuracy of 92.2% and an F1-score of 93%. Comparative results indicate that our model significantly outperforms baseline SVM and standard deep learning approaches. Furthermore, the architecture exhibits high computational efficiency and rapid convergence, highlighting its potential as a deployable engine for real-time mental health monitoring in clinical scenarios.

Based on findings in cross-lagged panel network (CLPN) models, Ma et al. concluded prospective effects between indicators of mindfulness and mental health problems. Here, we used multiverse methodology and found discrepant increasing, decreasing, and null effects depending on the used model, and meta-analytic aggregations of these discrepant effects did not differ significantly from zero. Hence, the conclusions by Ma et al. can be challenged. It is important for researchers to bear in mind that correlations, including cross-lagged effects in CLPN models, do not prove causality in order not to overinterpret findings, something that may have happened to Ma et al. For increased analytic rigor, we recommend researchers to fit, as we did here, alternative models to data and to juxtapose findings.

Diabetes-related foot disease represents a growing burden on healthcare services. Peripheral arterial disease (PAD) is a contributing factor in over half of the cases, with treatment of severe PAD through revascularisation being crucial for limb salvage. The Society for Vascular Surgery Wound, Ischaemia, foot Infection (WIfI) classification system enhances diagnosis by providing a framework for identifying high-risk individuals needing intervention. Decision-making regarding which strategy of revascularisation (angioplasty or surgical bypass) is most suitable in these patients is complex, with decisions being primarily guided by the anatomical pattern of the disease, patient fitness, and availability of autologous vein. This review aims to provide a summary of the assessment and management of patients with diabetes-related foot disease and PAD, discussing the factors that influence patient selection for revascularisation. In general, short-segment disease is best treated by an endovascular-first approach, while long-segment occlusions are better managed with open surgery. Ultimately, individuals should be assessed and managed in conjunction with a multi-disciplinary team as part of a holistic management strategy.

Early identification of high-risk individuals is essential to guide infection-prevention strategies and optimize antibiotic stewardship in this vulnerable population.

To identify independent risk factors associated with hospital-acquired infections in elderly ICU patients following antibiotic use and to develop and internally validate a clinical risk prediction model for early infection detection.

A retrospective cohort study was conducted in the ICU of Nanjing First Hospital, Nanjing Medical University. A total of 120 patients aged ≥65 years, with ICU stay >48 hours, no documented infection at ICU admission and antibiotic exposure within 48 hours before or at ICU admission were included. Demographic data, comorbidities, Sequential Organ Failure Assessment (SOFA) scores, antibiotic exposure characteristics, invasive device use and nutritional support were collected from electronic health records.

Hospital-acquired infections occurred in 46 patients (38.3%). Independent predictors included advanced age (odds ratio [OR] 1.08 per year), higher SOFA score (OR 1.25 per point), diabetes mellitus (OR 1.45), chronic kidney disease (OR 1.65), use of central venous catheters (OR 1.75), mechanical ventilation (OR 1.85), Foley catheterization (OR 1.55), broad-spectrum antibiotic use (OR 1.50), longer antibiotic duration (OR 1.20 per day) and prolonged ICU stay (all p<0.05). The prediction model demonstrated good discrimination (AUC-ROC = 0.82), which improved slightly after variable refinement (AUC-ROC = 0.83). Cross-validated performance remained robust (AUC = 0.80).

A multivariable risk prediction model using routinely available clinical parameters demonstrated good internal validity and may assist clinicians in early identification of high-risk patients, enabling targeted infection prevention and improved antibiotic stewardship.

Gestational diabetes mellitus (GDM) is a frequent pregnancy complication associated with negative maternal and neonatal outcomes. However, the contribution of non-glycaemic biochemical markers to pregnancy outcomes remains unclear. This study aimed to compare biochemical markers and clinical outcomes in women with and without GDM and to identify associations between these markers and adverse pregnancy outcomes (APOs).

In this prospective cohort study, 246 pregnant women at Shandong Provincial Third Hospital were divided into GDM (n = 123) and non-GDM (NGDM; n = 123) groups. Fasting glucose, HbA1c, lipid profile, liver and kidney function markers, and OGTT values were assessed. Pregnancy outcomes, including caesarean section, macrosomia, and premature rupture of membranes (PROM), were recorded. Multivariable logistic regression was used to determine associations between biochemical markers and outcomes, adjusting for age, BMI, and gestational weight gain.

GDM women had significantly higher fasting glucose levels, HbA1c, gestational BMI, and caesarean section rates (p < 0.001). Serum albumin levels were slightly higher in the GDM group (p = 0.028), whereas alkaline phosphatase (ALP) and direct bilirubin were higher in NGDM women. Higher serum albumin levels were associated with lower odds of macrosomia (AOR = 0.43, 95% CI: 0.20-0.93) and PROM in NGDM women. Creatinine was also inversely related to macrosomia risk in NGDM (AOR = 0.75, 95% CI: 0.60-0.94).

Distinct biochemical profiles were observed between GDM and NGDM pregnancies. Albumin and creatinine may serve as simple, cost-effective indicators of reduced obstetric risk among normoglycaemic women. Incorporating these routinely measured markers into prenatal screening could improve individualized risk prediction and early intervention strategies..

Insulin resistance and impaired insulin secretion are hallmarks of type 2 diabetes (T2D) and may influence risks of complications including dementia. We investigated dementia risk across T2D subgroups defined by beta-cell function and insulin sensitivity.

We used Homeostasis Model Assessment-2 indices of beta-cell function (HOMA2-B) and insulin sensitivity (HOMA2-S) to classify 7221 individuals with recently diagnosed T2D into insulinopenic (low HOMA2-B, high HOMA2-S), classical (low HOMA2-B, low HOMA2-S), and hyperinsulinemic (high HOMA2-B, low HOMA2-S) subgroups. Incident dementia was ascertained by validated hospital diagnosis codes and dementia-specific medication over 13 years. Absolute risks were estimated using the Aalen-Johansen estimator and adjusted hazard ratios (aHRs) using Cox regression.

Over a median follow-up of 9 years, 179 (2.5%) developed dementia. The 10-year risk (95% CI) was 3.8% (2.4%-5.8%) in the insulinopenic subgroup versus 2.8% in both classical (2.3%-3.5%) and hyperinsulinemic (2.0%-3.8%) subgroups. Compared with classical T2D, aHRs (95% CI) were 1.31 (0.83-2.09) for insulinopenic and 1.10 (0.78-1.54) for hyperinsulinemic T2D. No robust associations with dementia were observed with insulin resistance (HOMA-IR) or C-peptide levels, although compared to the lowest C-peptide levels (quartile 1), aHRs (95% CI) were decreased at 0.67 (0.45-1.01) in quartile 2, 0.73 (0.48-1.09) in quartile 3, and 0.89 (0.59-1.33) in quartile 4.

We found no clear associations between T2D subgroup, insulin resistance, or C-peptide level at T2D diagnosis and dementia risk. The numerically higher risk in those with lower insulin secretion was statistically imprecise and warrants further study.

BackgroundMetformin has been proposed to have neuroprotective benefits, but its effects on AD-related brain changes remain unclear and may be influenced by apolipoprotein E ε4 (APOE4) genotype, a major genetic risk factor for AD.ObjectiveTo examine the association between metformin use and in vivo AD pathologies and to evaluate whether APOE4 status moderates these associations in older adults with type 2 diabetes mellitus (T2DM).MethodsThis cross-sectional study used baseline data from 76 non-demented older adults with T2DM (aged 55-90 years), who were enrolled in the Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer's Disease (KBASE). The participants underwent comprehensive clinical and neuropsychological assessment and multimodal neuroimaging, including global amyloid- β (Aβ) retention ([¹¹C] PiB-PET), inferior temporal tau deposition ([¹⁸F] AV-1451 PET), AD-signature cortical thickness (AD-CT), and white matter hyperintensity (WMH) volume. Global cognition was assessed using the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) neuropsychological battery.ResultsAmong 76 participants, 55 (72%) were metformin users and 21 (28%) were non-users. Metformin use was significantly associated with greater AD-CT, but not with Aβ, tau, or WMH volume. A significant interaction between metformin use and APOE4 status was observed with respect to AD-CT. In APOE4-stratified analyses, metformin use was significantly associated with greater AD-CT and better global cognition among APOE4 non-carriers, but not among carriers.ConclusionsOur findings indicate that metformin use is associated with greater AD-CT-independently of amyloid or tau pathology-particularly among APOE4 non-carriers, and this structural preservation is accompanied by better cognitive outcomes.

This review presents an outline of the state of the knowledge on the prevention and diagnosis of cervical cancers over the last decade. Screening and prevention methods are considered, such as cervical self-sampling, Human Papillomavirus (HPV) vaccination and the use of digital technologies and artificial intelligence (AI) in diagnostics and screening, as are some success stories. However, despite the successes stemming from the UK and Europe-such as that no new cases of cervical cancer have been detected in a cohort of Scottish women vaccinated against HPV between 12-13 years old-cervical screening rates are falling and social, cultural and economic barriers to HPV vaccination uptake remain. There are several clear pathways that could reduce not only incidence rates of cervical cancer, but also non-cervical HPV related cancers such as oropharyngeal and anal cancers.

Small round blue cell tumors are a heterogeneous group of aggressive pediatric neoplasms that can radiologically and clinically mimic infectious or inflammatory conditions, including tuberculous meningitis (TBM). Differentiating between these entities is crucial, as delays in diagnosis may significantly affect outcomes.

An 8-year-old previously healthy boy presented with acute lower extremity weakness, inability to ambulate, and urinary retention following a recent urinary tract infection. Neurological examination revealed symmetric distal weakness and areflexia. Cerebrospinal fluid analysis showed markedly elevated protein levels without pleocytosis, consistent with albuminocytologic dissociation, and Guillain-Barré syndrome was diagnosed. Intravenous immunoglobulin therapy was initiated; however, no clinical improvement was observed. During hospitalization, the patient developed seizures and signs of increased intracranial pressure. Craniospinal magnetic resonance imaging revealed hydrocephalus and multiple contrast-enhancing lesions involving the suprasellar region, brainstem, and cerebral hemispheres. Despite extensive infectious and inflammatory workup, no alternative diagnosis was identified initially. Brain biopsy ultimately demonstrated a CD56- and synaptophysin-positive small round blue cell tumor, consistent with medulloblastoma. This case highlights a rare presentation of medulloblastoma mimicking TBM and underscores the importance of reconsidering the diagnosis in patients with atypical features or poor response to standard therapy.

This case demonstrates that the extremely rare leptomeningeal spread of medulloblastoma can clinically and radiologically mimic TBM, posing a significant diagnostic challenge in pediatrics. In the absence of systemic signs of tuberculosis, lack of response to treatment, and the presence of progressive neuroimaging abnormalities, the diagnosis should be reconsidered. Early histopathological confirmation is essential to ensure the timely initiation of oncological treatment.